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Stable IHD - Coggle Diagram
Stable IHD
Oral Nitrates
Nitroglycerin
Dosing (oral)
:Initial 2.5 to 6.5 mg 3 to 4 times daily; increase dose as needed based on response and tolerability to 26 mg 4 times daily. Include a nitrate-free interval of ~10 to 12 hours each day to minimize the risk of tolerance.
MOA
: NO > activation cGMP > smooth muscle relaxation > dilates coronary arteries and improves collateral flow to ischemic regions
CI
: hypersensitivity reaction, pts taking a phosphodiesterase 5 (PDE5) inhibitor (severe hypotension), acute circulatory failure or shock, early MI, increased intracranial pressure; severe anemia.
AEs
: headache, hypotension, peripheral edema, syncope, paradoxical bradycardia and increased angina pectoris may accompany hypotension
Dosage Forms
: aerosol solution, ER capsule, ointment (trandermal, rectal), sublingual packet, transdermal patch 24 h, solution (IV, translingual), sublingual tablet
PK
t1/2: ~1 to 4 minutes
E: urine (as Inactive metabolites)
Onset of action:
Sublingual tablet: 1 to 3 minutes
Translingual spray: Similar to sublingual tablet
Extended release: ~60 minutes
Topical: 15 to 30 minutes
Transdermal: ~30 minutes
IV: Immediate
D: ~3 L/kg
Protein binding: 60%
M: Extensive first-pass effect; metabolized hepatically to glycerol di/mononitrate metabolites via liver reductase enzyme; subsequent metabolism to glycerol and organic nitrate; nonhepatic metabolism via red blood cells and vascular walls also occurs
stored In dark, glass containers!
Isosorbide dinitrate
MOA
: NO > activation cGMP > smooth muscle relaxation >vasodilator effect on peripheral veins and arteries, reducing oxygen demand by decreasing preload. Also, dilates coronary arteries and improves collateral flow to ischemic regions
PK/PD/PGx
M: extensively hepatic, conjugated to active metabolits
Onset: Sublingual, 2-5 minutes, oral: ~1 hour
Highly variable F, increases with chronic therapy
Warnings/Precautions
Increased intracranial pressure
Hypotension/bradycardia
Hypertrophic Cardiomyopathy
Contraindications
Hypersensitivity
Concurrent PDE inhibitor use
Concurrent riociguat
Monitoring: BP, HR
DDIs
BP lowering agents
3A4 Inducers/Inhibitors
Nitric Oxide
PDE Inhibitors
ADR
Hypotension
Headache
Special Pops
Geriatric: Administer lowest recommended dose and titrate upwards
Education
Used to prevent chest pain, not treat while it's happening
BP Monitoring
Orthostatic hypotension
Isosorbide mononitrate
MOA
: NO > activation cGMP > smooth muscle relaxation >vasodilator effect on peripheral veins and arteries, reducing oxygen demand by decreasing preload. Also, dilates coronary arteries and improves collateral flow to ischemic regions
PK/PD/PGx
A: Rapid and complete
100% F
V:~0.5 L/kg
M: Hepatic
E: Urine
Onset 30 to 45 minutes
Dosage
IR: 20 mg BID (7 hours apart)
ER: 30 mg to 60 mg QD in morning
Contraindications
Hyperesnsitivity
Concurrent PDE-5 inhibitors
Riociguat
Warnings/Precautions
Hypotension/Bradycardia
Increased Intracranial Pressure
Hypertrophic Cardiomyopathy
Monitoring
BP/HR
DDIs
PDE-5 inhibitors
Riociguat
BP Lowering Meds
CYP 3A4 Inducers/Inhibitors
ADR
Headaches, dizziness
Special Pops
Geriatrics: Initiate lowest dose recommended
Education
Prevents chest pain, not to treat it as it happens
BP Monitoring
Goals
Prevent episodes of angina
Reduce CV risk/morbidity/mortality
Improve QOL and ADL
Antiplatelets
Aspirin
MOA: Irreversible blocks COX-1 activity for the life of the platelet (~10 days), inhibiting Thromboxane 2 production, leading to reduced platelet activation and aggregation
Contraindications
Hypersensitivity/Aspirin Allergy
DDI
NSAIDs (reduced therapeutic effect)
Drugs w/bleeding risk (warfarin, DOACs, SSRIs, etc.)
Antidiabetics (Hypoglycemia)
ACEis/ARBs (pain/fever dosing)
Dose: 75 to 100 mg Daily (often supplied in 81 mg tabs)
Warnings/Precautions
Hypoglycemia
Gout
Heavy, chronic alcohol use
GI Bleeds
PUD
Surgery (stop at least 5 days before)
Renal/Hepatic Impairment
ADR
GI Ulcers
Hypersensitivity
PK/PD/PGx
Rapid Absorption
Vd; 10L
Hydrolyzed to salicylate by ester aces in GI Mucosa (ProDrug)
Salicylate metabolized by hepatic conjugation
Excretion: Urine (&5% salicylic acid, 10% salicylic acid)
Antiplatelet effects last life time of platelets (10 days)
Irreversible inhibition
Special Populations
Dose adjustments in renal/hepatic impairment
Education/Counseling
Tell your doctor about this drug before a procedure
Hypersensitivity
Monitoring
S/Sx of bleeding
P2Y12 Inhibitors
Boxed Warnings
Clopidogrel: Diminished antiplatelet effect in patients with 2 loss of function alleles of CYP2C19 gene
Prasugrel/Ticarelor: Bleeding Risk
Contraindications
Hypersensitivity to any drug in the class
Pathological bleeding
Prior TIA or Stroke (Prasugrel)
History of intracranial hemorrhage (ticagrelor)
Hematopoietic disorders
ADR
Bradycardia
Hypotension
Dizziness
Headache
Pruritus, rash
Nausea
Leukopenia
Hemorrhage (Major, Minor, GI)
Dyspnea
MOA: Block the component of the P2Y12 ADP receptor on the platelet surface, prevents activation of the GPIIb/IIIa receptor complex reducing platelet activation and aggregation
Clopidogrel, prasugrel, ticlopidine irreversibly inhibit aggregation, affect platelets for 7-10 days
Ticagrelor reversible antagonizes the receptor, recovery depends on serum concentrations
Cangrelolr binds selectively and reversibly
PK/PD/PGx
Clopidogrel and Presugral are Pro-Drugs
Onset of Action varies (from 2 minutes (Cangrelor) to days for onset of Clopidogrel
Duration of action between 5-10 days
Highly protein bound
Metabolism
Esterase mediated hyrolysis to inactive metabolite
Prasugrel: 3A4 and 2B6 to active metabolite
Clopidogrel: 2C19 to active metabolite
Ticagrelor: 3A4
Special Populations: don't use Clopidogrel in 2C19 PM
Education
S/Sx of bleeding
Monitoring
S/Sx of bleeding
Dosages
Clopidogrel: 75 mg QD
Non-pharm
Revascularization (severe cases)
Lifestyle modification
Goal Monitoring
Frequency of angina
Pt. ADL and function